INTERACTION OF SECRETIN-5-27 AND ITS ANALOGS WITH HORMONE RECEPTORS ON PANCREATIC ACINI

The C-terminal tricosapeptide of secretin (S5-27) and 2 analogs, one with Asn replacing Asp in position 15 (15-Asn-S5-27) and one with Lys replacing Asp in position 15 (15-Lys-S5-27) were tested for their abilities to interact with hormone receptors on [guinea pig] pancreatic acinar cells. In interacting with the receptors which prefer vasoactive intestinal peptide (VIP-preferring receptors), the apparent affinity of 15-Asn-S5-27 was equal to that of 15-Lys-S5-27 and was greater than that of S5-27. In interacting with secretin-preferring receptors, the apparent affinity of 15-Asn-S5-27 was equal to that of S5-27 and was greater than that of 15-Lys-S5-27. In interacting with the secretin-preferring receptors each of the secretin fragments was approximately 2% as effective as secretin in causing an increase in cellular cyclic[c]AMP. None of these fragments was able to cause a detectable increase in cAMP mediated by the VIP-preferring receptors. The dose vs. response curves for the action of secretin and vasoactive intestinal peptide on cellular cAMP and on amylase secretion as well as the pattern of effects of secretin fragments on these actions indicated that the increase in amylase secretion caused by VIP and secretin is mediated exclusively by the VIP-preferring receptors. Occupation of approximately 50% of the VIP-preferring receptors is sufficient to cause maximal stimulation of amylase secretion.